ns
There have been reports of severe hepatic reactions including acute liver failure in patients receiving TNF-blockers. In controlled Phase 3 trials of Humira (40 mg SC every other week) in patients with RA, PsA, and AS with control period duration ranging from 4 to 104 weeks, ALT elevations ≥ 3 x ULN occurred in 3.5% of Humira-treated patients and 1.5% of control-treated patients. Since many of these patients in these trials were also taking medications that cause liver enzyme elevations (e.g., NSAIDS, MTX), the relationship between Humira and the liver enzyme elevations is not clear. In controlled Phase 3 trials of Humira (initial doses of 160 mg and 80 mg, or 80 mg and 40 mg on Days 1 and 15, respectively, followed by 40 mg every other week) in patients with CD with control period duration ranging from 4 to 52 weeks, ALT elevations ≥ 3 x ULN occurred in 0.9% of Humira-treated patients and 0.9% of control-treated patients. In controlled Phase 3 trials of Humira (initial doses of 160 mg and 80 mg on Days 1 and 15 respectively, followed by 40 mg every other week) in patients with UC with control period duration ranging from 1 to 52 weeks, ALT elevations ≥3 x ULN occurred in 1.5% of Humira-treated patients and 1.0% of control-treated patients. In controlled Phase 3 trials of Humira (initial dose of 80 mg then 40 mg every other week) in patients with Ps with control period duration ranging from 12 to 24 weeks, ALT elevations ≥ 3 x ULN occurred in 1.8% of Humira-treated patients and 1.8% of control-treated patients.
Immunogenicity
Patients in Studies RA-I, RA-II, and RA-III were tested at multiple time points for antibodies to adalimumab during the 6- to 12-month period. Approximately 5% (58 of 1062) of adult RA patients receiving Humira developed low-titer antibodies to adalimumab at least once during treatment, which were neutralizing in vitro. Patients treated with concomitant methotrexate (MTX) had a lower rate of antibody development than patients on Humira monotherapy (1% versus 12%). No apparent correlation of antibody development to adverse reactions was observed. With monotherapy, patients receiving every other week dosing may develop antibodies more frequently than those receiving weekly dosing. In patients receiving the recommended dosage of 40 mg every other week as monotherapy, the ACR 20 response was lower among antibody-positive patients than among antibody-negative patients. The long-term immunogenicity of Humira is unknown.
In patients with JIA, adalimumab antibodies were identified in 16% of Humira-treated patients. In patients receiving concomitant MTX, the incidence was 6% compared to 26% with Humira monotherapy.
In patients with AS, the rate of development of antibodies to adalimumab in Humira-treated patients was comparable to patients with RA.
In patients with PsA, the rate of antibody development in patients receiving Humira monotherapy was comparable to patients with RA; however, in patients receiving concomitant MTX the rate was 7% compared to 1% in RA.
In patients with CD, the rate of antibody development was 3%.
In patients with moderately to severely active UC, the rate of antibody development in patients receiving Humira was 5%. However, due to the limitation of the assay conditions, antibodies to adalimumab could be detected only when serum adalimumab levels were < 2 ug/ml. Among the patients whose serum adalimumab levels were < 2 ug/ml (approximately 25% of total patients studied), the immunogenicity rate was 20.7%.
In patie |
